Mitochondrial Protection Promoted by the Coffee Diterpene Kahweol in Methylglyoxal-Treated Human Neuroblastoma SH-SY5Y Cells

  • Marcos Roberto de OliveiraEmail author
  • Izabel Cristina Custódio de Souza
  • Cristina Ribas Fürstenau
Original Article


The coffee diterpene kahweol (KW; C20H26O3) is a cytoprotective agent exhibiting potent antioxidant actions, as demonstrated in several experimental models. In spite of the efforts to elucidate exactly how KW promotes cytoprotection, it was not previously examined whether KW would be able to protect mitochondria of human cells undergoing redox stress. In the present work, we have treated the human neuroblastoma SH-SY5Y cell line with KW at 0.1–10 μM for 12 h prior to a challenge with methylglyoxal (MG), a reactive dicarbonyl that impairs mitochondrial function. We have found that KW at 10 μM suppressed the loss of mitochondrial membrane potential (MMP) and the bioenergetics decline (including decreased activity of the mitochondrial complexes I and V and reduced production of adenosine triphosphate, ATP) in the MG-treated SH-SY5Y cells. KW also prevented the MG-elicited generation of reactive oxygen and nitrogen species (ROS and RNS, respectively) in the SH-SY5Y cells. In this regard, KW exerted an antioxidant effect on the membranes of mitochondria obtained from the MG-treated cells. The mitochondria-related effects induced by KW were blocked by inhibition of the phosphoinositide 3-kinase (PI3K)/Akt or of the p38 mitogen-activated protein kinase (MAPK) signaling pathways. Moreover, silencing of the transcription factor nuclear factor E2-related factor 2 (Nrf2) suppressed the mitochondrial protection promoted by KW in the MG-challenged cells. Therefore, KW protected mitochondria by a mechanism associated with the PI3K/Akt and p38 MAPK/Nrf2 signaling pathways.


Kahweol Mitochondria Methylglyoxal Cytoprotection Antioxidant Nrf2 



MRO receives a “Bolsa de Produtividade em Pesquisa 2-PQ2” fellow from the Conselho Nacional de Pesquisa e Desenvolvimento Tecnológico (CNPq) (protocol number 301273/2018-9). This research was supported by CNPq (protocol numbers 400216/2016-7 and 460903/2014-4).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12640_2019_107_MOESM1_ESM.pdf (131 kb)
Figure S1 The effects of methylglyoxal (MG) and/or kahweol (KW) on the release of cytochrome c to the cytosol (A), caspase-9 activity (B), caspase-3 activity (C), DNA fragmentation levels (D), and cleaved PARP levels (E) in SH-SY5Y cells. KW at 10 μM was administrated to the cells for 12 h prior to the exposure to MG at 500 μM for further 24 h. Data are demonstrated as the mean ± SD of three or five independent experiments each done in triplicate. One-way ANOVA followed by the post hoc Tukey’s test, *p < 0.05 vs control cells, #p < 0.05 vs MG-treated cells. (PDF 130 kb)
12640_2019_107_MOESM2_ESM.pdf (50 kb)
Figure S2 The effects of the transfection with small interfering RNA (siRNA) targeting Nrf2 on the nuclear content of Nrf2 in SH-SY5Y cells treated with kahweol (KW). Nrf2 was silenced by using small interfering RNA (siRNA) for 48 h before KW treatment. Data are demonstrated as the mean ± SD of three or five independent experiments each done in triplicate. One-way ANOVA followed by the post hoc Tukey’s test, *p < 0.05 vs control cells transfected with negative control (NC) siRNA; #p < 0.05 vs the kahweol-treated cells transfected with NC siRNA. (PDF 49 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Grupo de Estudos em Neuroquímica e Neurobiologia de Moléculas BioativasUniversidade Federal de Mato Grosso (UFMT)CuiabaBrazil
  2. 2.Programa de Pós-Graduação em Química (PPGQ)Universidade Federal de Mato Grosso (UFMT)CuiabaBrazil
  3. 3.Programa de Pós-Graduação em Ciências da Saúde (PPGCS)Universidade Federal de Mato Grosso (UFMT)CuiabaBrazil
  4. 4.Programa de Pós-Graduação em Bioquímica e Bioprospecção (PPGBBIO), Centro de Ciências Químicas, Farmacêuticas e de Alimentos (CCQFA), Instituto de BiologiaUniversidade Federal de Pelotas (UFPel)PelotasBrazil
  5. 5.Centro de Ciências Naturais e HumanasUniversidade Federal do ABCSanto AndréBrazil

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